Two pilot studies were initiated in the development of a human papillomavirus infectivity and disease model using rhesus macaque females previously infected with SIV. In study I, two otherwise healthy females having previously been inoculated intravaginally with SIV, were given intravaginal inoculations with HPV-11 produced using the nude mouse xenograft system. Both animals developed antibodies capable of binding purified HPV-11 virions and baculovirus-expressed HPV-11 11-VLPS. Both animals developed HPV-11 neutralizing antibodies as demonstrated using an in vivo infectivity assay for HPV-11. The kinetics of the immune response and delayed production of antibodies recognizing conformationally-dependent epitopes for HPV-11 suggested productive infection. Ten months after infection, tissues obtained at necropsy were tested by in situ hybridization and PCR for persistent HPV-11 nucleic acids. Results were negative and no condyloma was observed. In study II, SIV-infected rhesus females were given intravaginal inoculations of infectious HPV-11 or HPV-11 inactivated by G-irradiation. Although no antibody responses were observed through 3 months after HPV-11 inoculation, PCR studies on cellular material obtained by periodic vaginal lavage showed persistence of HPV-11 DNA within the animals receiving infectious but not G-irradiated HPV-11. Retrospective analysis of the infectious titer of the HPV-11 stock used in study II demonstrated a titer approximately 100-fold lower than that used in study I, although the protein component was at least equivalent to that used in pilot study I. These studies suggest the SIV-infected rhesus female may serve as a host for at least transient genital tract infection by HPV-11.